Synthesis, cytotoxic evaluation, and<i> in</i><i> silico</i> studies of novel benzenesulfonamide-thiazolidinone derivatives against colorectal carcinoma

ZENGİN KURT B., GÖKÇE M., ŞENOL H., ÖZTÜRK CİVELEK D., Dandin G., Gazioglu I.

JOURNAL OF MOLECULAR STRUCTURE, cilt.1321, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1321
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.molstruc.2024.140153
  • Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Thirteen new benzenesulfonamide derivatives containing 4-thiazolidinone were synthesized. Their cytotoxic properties were tested on colorectal carcinoma (HT-29, DLD-1, COLO-205) and normal colon fibroblast (CCD986Sk) cell lines. Compounds 3l (IC50=114.62 50 =114.62 mu M), 3a (IC50=25.82 50 =25.82 mu M), 3k (IC50=30.99 5, and 3i (IC50=62.94 50 mu M) showed the highest cytotoxicity on HT-29, DLD-1, COLO-205, and CCD-986Sk cell lines, respectively. Compound 3e (IC50=1075.4 50 =1075.4 mu M) exhibited the least cytotoxicity against CCD-986Sk. The apoptosis profile of 5-FU at 5 mu M was similar to that of compound 3e at 30 mu M. Molecular docking and MD simulations showed stable interactions for compounds 3i and 3e . Molecular docking and MD simulations revealed that compounds 3i and 3e exhibit stable interactions with key cancer-related protein targets, particularly TGF(32.These interactions suggest their potential as therapeutic agents. The predicted ADME parameters further highlighted compounds 3e and 3i for their favorable lipophilicity, solubility, permeability, and oral absorption profiles, supporting their promise as candidates for future drug development.